EXPRESSION AND FUNCTION OF THE GAMMA(C) SUBUNIT OF THE IL-2, IL-4, AND IL-7 RECEPTORS - DISTINCT INTERACTION OF GAMMA(C) IN THE IL-4 RECEPTOR

IL-2R, IL-4R, and IL-7R share a common subunit referred to as gamma(c) and the IL-13R has been proposed to contain gamma(c) as a subunit. In this report we have used two novel mAbs (3E12 and 4G3) to distinct ep itopes of mouse gamma(c) to determine its lymphoid cell distribution a nd to examine whether gamma(c) uses similar epitopes to interact with different cytokines and cytokine receptors. FACS analysis revealed tha t gamma(c) is expressed in most lymphocytes, myeloid cells, embryonic thymocytes, and lymphoid cell lines. Results from radiolabeled ligand binding studies, biochemical analysis of ligand-receptor cross-linked complexes, and cytokine bioassays indicate that the epitope defined by mAb 4G3 closely defines the IL-7 binding region of gamma(c) and overl aps the IL-2 binding region of gamma(c). These studies also indicate t hat gamma(c) interacts with IL-4 in the context of the IL-4R in a mann er that is distinct from its role in the IL-2R and 1L-7R and suggest t hat the 3E12 epitope defines a region of gamma(c) that intimately inte racts with the IL-4R. The B9 plasmacytoma, which proliferates in respo nse to IL-4 and IL-13, was shown to not express gamma(c). Thus, at lea st in some circumstances, gamma(c) is dispensable for signaling via th e IL-4R and is not a required subunit of the IL-13R.